Every animal cell contains a nucleus in which the genetic material (DNA) is stored, replicated, and accessed as needed for the synthesis of cell- specified proteins. While much is known about nuclear events at the molecular level, we are fundamentally ignorant of its larger-scale levels of organization, and this ignorance is impeding our ability to understand how the cell operates. The recognition by the biomedical research community that our ability to combat disease is directly linked to our knowledge of the basic operations of the cell, provides the impetus for and significance of these efforts to understand nuclear architecture. The aim is to observe the inner structures of the nucleus in its native hydrated state by rapid freezing followed by sectioning and observation of the frozen sections in the electron microscope. This is in contrast to conventional methods where water must be removed before observation, or components first isolated. These cryo-methods, which are technically demanding, and in use a few places in the world will be of long-term use in studying a variety of nuclear structures and processes.